Project Summary While several innovative and creative immuno-oncology (IO) strategies have shown promising results, a significant expansion of their clinical use will require collaborative efforts to elucidate the resistance mechanism, discover new immune targets, identify predictive biomarkers, evaluate combination therapies, and develop preventive approaches. Utilizing a multi-disciplinary team approach, we will support Immuno-Oncology Translation Network (IOTN)-funded components to discover new immune targets and evaluate novel immune- based therapies and combination approaches that eliminate established cancers in adults or to prevent cancers before they occur. Our DMRC strategy is to serve as an administrative and analytic hub at every step of the IOTN's translational studies, focusing to reduce the barrier for access to analytic expertise, improve the productivity of IOTN investigators, maintain a high standard for data collection and management, design and perform rigorous analytical strategies, and foster a collaborative and supportive research community. An experienced, multidisciplinary team has been assembled to pursue four specific aims: First, we will provide a centralized administration infrastructure to coordinate IOTN activities, building upon the NRG Oncology Statistical and Data Coordinating Center's experience of coordinating over 450 translational cancer studies across hundreds of participating sites. Second, we will provide multidisciplinary analytic expertise to support IOTN collaborative research, leveraging five of RPCI CCSG's shared resources: Biostatistics, Bioinformatics, Biomedical Data Science, Data Bank and BioRepository, and Immune Analysis. Our analytic support will be armed with professional IT staff and informed by an experienced IO researcher team. Third, we will develop innovative data integration methods to enhance IOTN research capacity, capitalizing on the well-respected Bioconductor project and the independent research programs of the RPCI department of Biostatistics and Bioinformatics. Fourth, we will actively promote the IOTN and engage in trans-consortium interactions, where we will leverage Bioconductor's decade-long experience in community engagement and the NRG data center's rich expertise in project coordination. Leveraging our active NCI-funded RPCI-committed resource to support the proposed multi-institutional trans-disciplinary IO research is not only cost-effective, but also flexible in its study-dependent scalability. Taken together, we envision that our DMRC, in close collaboration with the IOTN, will allow us to conduct highly effective and innovative translational studies to address the significantly unmet clinical needs related to IO.